Previous studies that have suggested an increased risk of autism among children of women who took antidepressants during pregnancy may actually reflect the known increased risk associated with severe maternal depression. In a study receiving advance online publication in Molecular Psychiatry, investigators from Massachusetts General Hospital (MGH) report that - while a diagnosis of autism spectrum disorder was more common in the children of mothers prescribed antidepressants during pregnancy than in those with no prenatal exposure - when the severity of the mother's depression was accounted for, that increased risk was no longer statistically significant. An increased risk for attention-deficit hyperactivity disorder (ADHD), however, persisted even after controlling for factors relating to a mother's mental health.

"We know that untreated depression can pose serious health risks to both a mother and child, so it's important that women being treated with antidepressants who become pregnant, or who are thinking about becoming pregnant, know that these medications will not increase their child's risk of autism," says Roy Perlis, MD, MSc, MGH Department of Psychiatry, senior author of the report.

The authors note that, while genetic factors are known to play a substantial role in autism, exactly how that risk may be exacerbated by environmental factors is not well understood. While animal studies and investigations based on health records have suggested an increased risk associated with prenatal antidepressant exposure, others found no such association. And since discontinuing antidepressant treatment significantly increases the risk of relapse - including an increased risk of postpartum depression - the current study was designed to clarify whether or not any increased autism risk could actually be attributed to the medication.

To investigate this possibility, the research team analyzed electronic health record data for children born at MGH, Brigham and Women's Hospital, or Newton Wellesley Hospital - hospitals belonging to Partners HealthCare System - for whom a diagnostic code for pervasive developmental disorder, a category that includes autism, was entered at least once between 1997 and 2010. They matched data for almost 1,400 such children with that of more than 4,000 controls with no autism diagnoses, born the same years and matched for a variety of demographic factors.

The children's information was paired with that of their mothers, noting any factors related to the diagnosis and treatment of major depression or other mental illness, including prescriptions for antidepressants and other psychotropic drugs. A similar analysis was done for almost 2,250 children with an ADHD diagnosis, compared with more than 5,600 matched controls with no ADHD diagnoses.

While prenatal exposure to antidepressants did increase the risk for either condition, in the autism-focused comparison, adjusting for factors indicating more severe maternal depression reduced the strength of that association to an insignificant level. Taking antidepressants with stronger action in the serotonin pathway, which has been suspected of contributing to a possible autism risk, did not increase the incidence of the disorder. In addition, the children of mothers who took a serotonin-targeting non-antidepressant drug for severe morning sickness had no increased autism incidence. Prescriptions for antipsychotic drugs sometimes used to treat severe, treatment-resistant depression, as well as psychotic disorders, did appear to increase the risk for autism. For ADHD, however, the increased risk associated with prenatal antidepressant exposure remained significant, although reduced, even after adjustment for the severity of maternal depression.

"There are a range of options - medication and non-medication - for treating depression and anxiety in pregnancy," says Perlis, an associate professor of Psychiatry at Harvard Medical School. "But if antidepressants are needed, I hope parents can feel reassured about their safety."

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $785 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.

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